Italy shocked former Six Nations champions France 23-18 in their opening match held at Rome's Olympic Stadium on Sunday.
Italy stunned France two years ago when they held on 22-21 at Stadio Flaminio in Rome.
Visitors France took the lead from Italy shortly before half time but Italy came back in the second half then after going ahead they held on for another famous victory.
The result means that now only Italy, England and Ireland can win the Six Nations with a Grand Slam.
Sergio Parisse finished off a fine move to give Italy an early lead at Rome's Stadio Olimpico but tries by Louis Picamoles and Benjamin Fall looked to have handed France the initiative.
However, a Martin Castrogiovanni try midway through the second half followed by a drop-goal by replacement out-half Kris Burton turned the match on its head and Italy held on to register only their third-ever win against France.
Parisse gave the home side the perfect start, crossing the French line after just four minutes after a superb line break by Luciano Orquera, who also knocked over the subsequent conversion.
Picamoles reduced the deficit to just two points when he powered over the Italian line after 11 minutes but an Orquera drop goal followed by a penalty saw the hosts open up an eight-point lead.
Yoann Huget crossed the Italian line with the help of the rest of the French backs after 26 minutes but was unable to ground the ball.
French out-half Frederic Michalak did manage to knock over a penalty shortly afterwards and after 33 minutes France scored their second try of the game when Fall took an inside pass from Huget to touch down.
Michalak stroked over the resultant conversion to send France in at half-time leading 15-13, and added another penalty on 49 minutes after Italy collapsed the scrum to move 18-13 head.
Italy refused to be overawed and moved back in front on 58 minutes thanks to a superb counter-attacking try by Castrogiovanni which was successfully converted by Orquera. Burton, on as a surprise replacement for Orquera, slotted over a drop-goal to leave France needing a converted try for victory.
Les Blues spent the last five minutes camped in the Italian 22 and although the home side finished the game with 14 men after prop Davide Giazzon received a yellow card, Italy held on for a famous win.
The Six Nations continues next weekend when Ireland welcome England to Dublin, France entertain Wales and Scotland take on Italy.
Final Score Italy 23 (13) France 18 (15)
Tries - Parisse, Castrogiovanni
Pen - Orquera
Con - Orquera 2
Drop - Orquera , Burton
Tries - Picamoles, Fall
Pen - Michalak 2
Con - Michalak
Referee: Nigel Owens
Italy (15-1) Andrea Masi (Wasps/ENG), Giovanbattista Venditti (Zebre), Tommaso Benvenuti (Treviso), Alberto Sgarbi (Treviso), Luke McLean (Treviso), Luciano Orquera (Zebre), Tobias Botes (Treviso), Sergio Parisse (Stade Francais/FRA - capt), Simone Favaro (Treviso), Alessandro Zanni (Treviso), Francesco Minto (Treviso), Quintin Geldenhuys (Zebre), Martin Castrogiovanni (Leicester/ENG), Leonardo Ghiraldini (Treviso) Andrea Lo Cicero (Racing Metro/FRA)
Replacements: Davide Giazzon (Zebre), Alberto De Marchi (Treviso), Lorenzo Cittadini (Treviso), Antonio Pavanello (Treviso), Paul Derbyshire (Treviso), Edoardo Gori (Treviso), Kristopher Burton (Treviso), Gonzalo Canale (La Rochelle/FRA)
(15-1)Yoann Huget (Toulouse); Wesley Fofana (Clermont), Florian Fritz (Toulouse), Maxime Mermoz (Toulon), Benjamin Fall (Racing Métro); Frederic Michalak (Toulon), Maxime Machenaud (Racing Métro); Louis Picamoles (Toulouse), Fulgence Ouedraogo (Montpellier); Thierry Dusautoir (Toulouse), Yoann Maestri (Toulouse), Pascal Papé (Stade Français, capt); Nicolas Mas (Perpignan), Dimitri Szarzewski (Racing Métro), Yannick Forestier (Castres)
Replacements: Benjamin Kaiser (Clermont), Vincent Debaty (Clermont), Luc Ducalcon (Racing Metro), Romain Taofifenua (Perpignan), Damien Chouly (Clermont), Morgan Parra (Clermont), Francois Trinh-Duc (Montpellier), Mathieu Bastareaud (Toulon)