Francis made the remarks during his weekly address at Saint Peter's Square in Vatican City on Sunday, urging Canadian political and Catholic religious leaders to "cooperate with determination” to shed light on the matter and to seek “reconciliation and healing”.
The discovery was announced by the chief of the Tk'emlups te Secwepemc First Nation — the home community of the Kamloops Indian Residential School— last month.
Chief Rosanne Casimir said they had found the remains of 215 children, some as young as three, buried on the grounds of the old school, near Kamloops, British Columbia.
The discovery sent shockwaves through Canadian society, especially as there were only 50 deaths officially on record there.
It also reopened wounds among indigenous survivors of colonial Canadian schools and fuelled outrage in Canada about the lack of information and accountability.
"I follow with pain the news coming from Canada about the shocking discovery of the remains of 215 children," Francis said, adding that he felt close to "the Canadian people, who have been traumatized by the shocking news."
"The sad discovery further increases awareness of the pain and suffering of the past," he added, calling for respect of the rights and cultures of native peoples.
"These difficult moments represent a strong reminder for all of us to distance ourselves from the model of colonizer ... and to walk side by side in dialogue and in mutual respect in the recognition of the rights and cultural values of all the sons and daughters of Canada," he said.
However, the pontiff did not go so far as to offer the direct apology that many people have been calling for.
Kamloops was one of the many boarding schools that were set up a century ago to forcibly assimilate Canada's indigenous people. It was established in 1890 under the leadership of the Roman Catholic Church, and closed in 1978.
The educational facility was part of a cross-Canada network of 139 residential schools created to forcibly assimilate indigenous children by removing them from their homes and communities, and forbidding them from speaking their native languages or performing cultural practices.
Canada’s residential school system forcibly separated more than 150,000 First Nations children from their families between 1831 and 1996.
The kids were subjected to abuse, malnutrition and rape in what the Truth and Reconciliation Commission tasked with investigating the system called “cultural genocide” in 2015.
In 2008, the Canadian government formally apologized for the system.
"Let us commend to the Lord the souls of all of the dead children in the residential schools of Canada and let us pray for the families and the native communities of Canada shattered by pain," the pontiff said before asking the crowd to join him in silent prayer.
Pope Francis remarks came after Canadian Prime Minister Justin Trudeau criticized the Catholic Church for ignoring its role in running many indigenous residential schools in the country following the recent discovery.
On Friday, Trudeau called on the Catholic Church to "take responsibility" and release records on indigenous residential schools under its direction after a mass grave was found at Kamloops.
The Canadian premier warned that his government was prepared to take "stronger measures," possibly including legal action, to obtain the documents demanded by victims' families if the church fails to comply.
"Before we have to start taking the Catholic Church to court, I am very hopeful that religious leaders will understand that this is something they need to participate in," Trudeau added.
He also stressed that, "We need to have truth before we can talk about justice, healing and reconciliation."
Also on Friday, the United Nations human rights experts called on both Canada and the Vatican to further investigate the deaths of the children found in Kamloops.
On Wednesday, Vancouver Archbishop J Michael Miller offered an apology on behalf of the church in a post on his Twitter account.
But there have been growing calls for an apology from Pope Francis himself.
No papal visit to Canada is scheduled.
A delegation of indigenous leaders had in 2009 met privately with Pope Benedict, who “expressed his sorrow” over the school harms to indigenous people.
Although the statement of regret was welcomed by the group as “significant,” they said it fell short of an official apology.
The Truth and Reconciliation Commission later noted that it was “disappointing to survivors and others that the Pope (had) not yet made a clear and emphatic public apology in Canada for the abuses.”
Pope Francis's subsequent refusal in 2018 -- after Canada's parliament passed a motion again asking the pontiff to apologize -- drew a polite rebuke from Trudeau, who said he was “disappointed” with the church's decision.
Taking office in 2015, Trudeau pledged to make Canada's almost 1.7 million indigenous people a priority of his government.
He said often that no relationship was more important to him than the one between Canada and indigenous communities.
Critics, however, say the mentions of indigenous issues in his stump speeches have either been brief or absent.