The Argentine pontiff addressed the European Parliament and Council of Europe during a lightning visit to Strasbourg, during which he called for urgent economic and social change.
Francis, the first non-European pope for more than a millennium, took a harsher tone than the last pontiff to visit the French city, John Paul II, in 1988 at the end of the Cold War.
"Europe seems to give the impression of being somewhat elderly and haggard, feeling less and less a protagonist," the 77-year-old pope told the European parliament.
Francis whose four-hour trip was the shortest abroad by any pope was critical of the growing nationalist and anti-immigration sentiment that has surged in Europe amid economic stagnation and unemployment.
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Yet he also seemed to echo some of the complaints by euro sceptic parties that won big in the European Parliament elections in May, when he criticised the EU for failing its citizens and being non-democratic.
"The great ideas which once inspired Europe seem to have lost their attraction, only to be replaced by the bureaucratic technicalities of its institutions," he said.
"We cannot allow the Mediterranean to become a vast cemetery," said the pope, who made a similar appeal during a visit to the Italian island of Lampedusa in 2013 after a major shipwreck.
"The boats landing daily on the shores of Europe are filled with men and women who need acceptance and assistance," he said.
Bells rang out from churches across Strasbourg to mark his visit, including the historic cathedral, where hundreds watched his speech on giant screens.