Paul Jedrasiak, Sébastien Bezy, Jonathan Danty and Virimi Vakatawa will all make their international debuts for France against Italy on Saturday.
Three more uncapped players – Camille Chat, Jefferson Poirot and Yacouba Camara – have all been named on the bench in a bold selection from new France head coach Guy Novès.
Only five players remain from the side who were thrashed by New Zealand in last year's Rugby World Cup quarter-final – Louis Picamoles, Yoann Maestri, and the front row of Rabah Slimani, Guilhem Guirado and Eddy Ben Arous.
Vakatawa was called up by France after impressing in the Dubai and Cape Town legs of the Sevens World Series.
Guilhem Guirado, the France hooker, is set for his first game as captain of les Bleus following the international retirement of Thierry Dusautoir.
France: 15 Maxime Médard, 14 Hugo Bonneval, 13 Gaël Fickou, 12 Jonathan Danty, 11 Virimi Vakatawa, 10 Jules Plisson, 9 Sébastien Bezy, 8 Louis Picamoles, 7 Damien Chouly, 6 Wenceslas Lauret, 5 Yoann Maestri, 4 Paul Jedrasiak, 3 Rabah Slimani, 2 Guilhem Guirado (c), 1 Eddy Ben Arous
Replacements: 16 Camille Chat, 17 Uini Atonio, 18 Jefferson Poirot, 19 Alexandre Flanquart, 20 Yacouba Camara, 21 Maxime Machenaud, 22 Jean-Marc Doussain, 23 Maxime Mermoz
Date: Saturday, February 6
Venue: Stade de France
Kick-off: 15:25 local (14:25 GMT)
Referee: JP Doyle (England)
Assistant Referees: George Clancy (Ireland), Federico Anselmi (Argentina)
TMO: Graham Hughes (England)