Full-back Brice Dulin replaces Scott Spedding while Fabien Sanconnie, 22, will make his debut in place of the injured Charles Ollivon.
Sebastien Vahaamahina has a back injury so Julien Le Devedec comes in, while Virimi Vakatawa is back on the wing.
France are only one place off the bottom having won only one of their first three games, against Scotland.
It will be the 40th occasion on which the sides have met in a competitive fixture, France winning 36 of their previous encounters and Italy three.
The Azzurri, who have conceded 132 points in their first three games of this year's competition, last beat France in 2013 at the Stadio Olimpico.
France: Brice Dulin; Noa Nakaitaci, Remi Lamerat, Gael Fickou, Virimi Vakatawa;  Camille Lopez, Baptiste Serin; Kevin Gourdon, Louis Picamoles, Fabien  Sanconnie; Yoann Maestri, Julien Le Devedec; Rabah Slimani, Guilhem Guirado  (capt), Cyril Baille.
Replacements: Christopher Tolofua, Uini Atonio, Eddy Ben Arous, Paul  Jedrasiak, Bernard Le Roux, Antoine Dupont, Francois Trinh-Duc, Yoann Huget.
France coach Guy Noves has made four changes for Saturday's Six Nations match with bottom side Italy in Rome.