The Ospreys have agreed to release the Welsh international from his current contract a year early having turned down a similar approach this time last season.
Byrne is the second Osprey to agree a French move in recent days after fellow Lion James Hook sealed a switch to Perpignan last week.
"I'll be sad to leave my home region but this was too good an opportunity for me to turn down at this stage of my career and I'm excited about what the future holds for me in France, and the challenges that lie ahead for me," said Byrne, who was the Lions' first-choice full back in South Africa a year-and-a-half ago before injury ended his tour prematurely.
"I'm extremely thankful to the Directors of the Ospreys for the way that they have handled this, allowing me to look ahead to what will be a fantastic experience for me.
"In the longer term, the Ospreys is my region and I'd like to think that I will be able to return here before my career is over."
The Ospreys hierarchy publicly suggested they may need to take a different approach with regards to star players after their Heineken Cup exit earlier this month.
Head coach Sean Holley pointed to the amount of time international players such as Byrne spend away from the region, an issue that would be further highlighted next season with the presence of the World Cup.
"First and foremost, the Ospreys are about developing local talent, and producing players not only for the region, but for the national team also. As such, it is extremely disappointing to lose a player who hails from the region, and who has been, and continues to be, an excellent servant to the Ospreys," said Ospreys managing director Mike Cuddy.
"Our determination to keep Lee at the Ospreys meant that we fought hard to keep him here, turning down a similar request twelve months ago, but unfortunately, the circumstances are such that we now find ourselves in this position where we have reluctantly agreed to release Lee, given his desire to take on a fresh challenge following the Rugby World Cup later this year.
"We would not have seen much of Lee next season, when he will be 31, and for him to have the security of a three-year contract and the change of lifestyle that this move will allow him is a fantastic personal opportunity and we wish him the best of luck. Between now and the end of the season, I have no doubt that he will continue to give the Ospreys the same unquestionable commitment he always has in his time with us."
Byrne joined the Ospreys from local rivals the Scarlets in the summer of 2006.
The former Bridgend player has made 89 appearances for the reigning Magners League Champions, scoring close to a try every three games.