In the back-line, Wesley Fofana returns to the run-on side to replace Gael Fickou at inside centre.
Fofana last played in France's opener against Wales but missed the matches against England, Scotland and Ireland due to injury.
This will be his final Six Nations Test after he announced in January that he will retire from international rugby after the 2019 Rugby World Cup in Japan.
In the only other back-line change, Maxime Medard slots in at full-back where takes over from Thomas Ramos, who drops down to the replacements bench.
In the forwards, Yacouba Camara and Gregory Alldritt take over from Arthur Iturria and Wenceslas Lauret as the starting flankers.
Iturria has been included on the bench as back-row cover.
In the second-row, Paul Willemse replaces Sebastien Vahaamahina while Etienne Falgoux will make his first Test start at loosehead prop after coming in for the injured Jefferson Poirot.
France: 15 Maxime Medard, 14 Damian Penaud, 13 Mathieu Bastareaud, 12 Wesley Fofana, 11 Yoann Huget, 10 Romain Ntamack, 9 Antoine Dupont, 8 Louis Picamoles, 7 Yacouba Camara, 6 Gregory Alldritt, 5 Paul Willemse, 4 Felix Lambey, 3 Demba Bamba, 2 Guilhem Guirado (c), 1 Etienne Falgoux
Replacements: 16 Camille Chat, 17 Dany Priso, 18 Dorian Aldegheri, 19 Paul Gabrillagues, 20 Arthur Iturria, 21 Baptiste Serin, 22 Camille Lopez, 23 Thomas Ramos
Date: Saturday, March 16
Venue: Stadio Olimpico, Rome
Kick-off: 13:30 local (12:30 GMT)
Referee: Matthew Carley (England)
Assistant Referees: Nigel Owens (Wales), Andrew Brace (Ireland)
TMO: Graham Hughes (England)