Francis denounced the carnage as a "gesture of war" carried out by blood-thirsty people beholden to the weapons industry during an Easter Week Mass with asylum-seekers at the shelter in Castelnuovo di Porto, outside Rome.
The Holy Thursday rite re-enacts the foot-washing ritual Jesus performed on his apostles before being crucified, and is meant as a gesture of service.
"We have different cultures and religions, but we are brothers and we want to live in peace," Francis said in his homily, delivered off-the-cuff in the windy courtyard of the centre.
Several of the migrants then wept as Francis knelt before them, poured holy water from a brass pitcher over their feet, wiped them clean and kissed them.
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Francis was greeted with a banner reading "Welcome" in a variety of languages as he walked down a makeshift aisle to celebrate the outdoor Mass.
Vatican rules had long called for only men to participate in the ritual, and past popes and many priests traditionally performed it on 12 Catholic men, recalling Jesus' 12 apostles and further cementing the doctrine of an all-male priesthood.
Francis shocked many Catholics within weeks of his 2013 election by performing the ritual on women and Muslims at a juvenile detention centre. After years of violating the rules outright, Francis in January changed the regulations to explicitly allow women and girls to participate.