"Please let us stop this shipwreck of civilization!" the Pope said at the Mytilene Reception and Identification Center, decrying the loss of life in the Mediterranean and countries that close their borders to refugees.
"We are living in the era of barbed wire and walls," Francis said, but the coronavirus pandemic has made us realize "we are all in the same boat."
"Let us stop ignoring reality," the Pope said, "stop constantly shifting responsibility, stop passing off the issue of migration to others."
The Mytilene camp currently holds about 2,000 refugees, many of them from Syria, Iraq, Afghanistan and Africa.
Hawar, a refugee from Iraq told CNN she has been stuck in camps on Lesbos for six years. Her applications for asylum, she said, are continually rejected while newer refugees from Afghanistan, she said, have already been transferred.
She said she is willing to go anywhere. "It was better in my country," she said. "Here it is like a prison."
Khaled a refugee from Syria, who is in a wheelchair, said he would like to ask the Pope why some people are more equal than others.
"We are hoping the Pope will listen; others don't listen. All families here have problems," he said.
Francis walked along the gravel streets of the camp and shook hands with some of the refugees lined up outside the storage containers they call home.
The Pope thanked the Greek residents of Lesbos for welcoming refugees, despite the strain it puts on their small island.
When the Pope visited in 2016, he brought back 12 refugees from Lesbos on his papal plane to Rome.
The government of Cyprus said Friday the Pope is arranging for 50 refugees to be transferred from Cyprus to Italy. The Vatican has confirmed 12 will be transferred in the coming weeks.
Francis winds up his five-day visit to Cyprus and Greece on Monday.