The filming of this and Mesrine Part 1: Killer Instinct (2008), which lasted nine straight months, was done in reverse chronological order so that Vincent Cassel could progressively lose the weight he gained in preparation of the role, as Cassel knew he couldn't gain weight while filming.
Producer Thomas Langmann first contacted Vincent Cassel about the Mesrine project in 2001, after the release of Jacques Audiard's Read My Lips (2001). Cassel initially accepted, but then bowed out as he found the script too "black and white". Benoît Magimel and 'Vincent Elbaz'convinced by new helmer 'Jean-Francois Richet' were then successively attached before Cassel returned' and especially Abdel Raouf Dafri's two-part script, claiming the screenwriter had succeeded in bringing the right tone to the picture and the character, bringing out all his darkness and paradoxes.
Benoît Magimel, who was at one time set to star, stepped down from the Mesrine project without informing producer Thomas Langmann, choosing instead to issue a press release. As a result of this a fight erupted on November 25th 2004 at the Intertalent talent agency between Langmann and Magimel's agent, François Samuelson, where Langmann headbutted Samuelson and broke his nose. Samuelson was on sick leave for nine days and pressed charges against Langmann.