Lyon were relegated from the Top 14 for the second time in three years after falling to a 28-10 defeat at Oyonnax.
Promoted last season, Lyon’s latest loss leaves them 10 points behind nearest rivals Castres and Bayonne with just one match to play.
Oyonnax consolidated their place in the leading six teams who make the play-offs in what would be a fantastic end of the season after dicing with relegation last year.
In their final match at their Charles-Mathon stadium under manager Christophe Urios, who will coach Castres next season, Oyonnax dominated under the rain despite falling behind to an early Romain Loursac penalty.
Lyon were hit by the sin-binning of South African Coenie Basson after 22 minutes, conceding two tries to Silvere Tian (23) and Alaska Taufa (31).
Oyonnax pushed their advantage to 18-3 at the break and picked up a bonus through a Benjamin Urdapilleta try on 59 minutes, although Deon Fourie crossed for the visitors after 73 minutes with Lachie Munro converting.
Making the end-of-season play-offs - and a place in next season's lucrative European Champions Cup - would be a remarkable achievement for Oyonnax, a team that represents a town of just 23,000 inhabitants in the unfashionable rugby area of eastern France.
The team only escaped relegation back to the ProD2 last season after finishing with a better points difference.
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