Background: Based on clinical data and the partially non-cross-resistance of oxaliplatin with other platinum compounds, this phase II trial evaluated the safety and efficacy of a modified FOLFOX6 regimen in pts with PRR OVCA with a platinum-free interval of less than 6 months after any previous platinum-containing line of therapy. Methods: From 10/2008 till 08/2013, a total of 43 eligible pts with measurable (RECIST) and/or evaluable (CA125) disease were included in this study and received a median number of 8 courses (range: 1-14) of a modified FOLFOX6 regimen consisting in oxaliplatin 85 mg/m² d1, L-leucovorin 200 mg/m² d1 followed by a continuous iv infusion of 5-FU 2600 mg/m²/48hrs every 2 weeks until disease progression or unacceptable toxicity. Pt characteristics: median age 57 years (range: 37-81), median PS 1 (0-2), serous histological subtype 60%, median number of previous lines 3 (1-12), prior exposure to carboplatin 100%, paclitaxel 98%, pegylated liposomal doxorubicin 63%, gemcitabine 23%, topotecan 23%, cyclophosphamide 14%, bevacizumab 9%. Results: Antitumor activity was seen in 35 cases with measurable disease: 1 CR + 15 PR, for an objective response rate of 46% (95%CI: 29-63%) and a median duration of response of 7.0 months (95%CI: 5.5-8.4 months); 13 SD (37%); 6 PD (17%). A clinical benefit rate (CR + PR + SD > 6 months) was observed in 21/43 (49%) pts (95% CI: 34-64%). Overall, the median time to progression was 5.8 months (95%CI: 4.9-6.5). Most side effects were moderate (G1&2): anemia in 88%, thrombocytopenia 67%, leucopenia 56%, neurological 81%, fatigue 72%, liver 51%, mucositis 41%, diarrhea 30%, renal 18%, hand-foot syndrome 9% of the pts. G3 toxicities included febrile neutropenia in 9%, neurological 9%, diarrhea 7%, mucosal 2% and liver toxicity 2% of the pts, leading to dose reductions in 13 pts (30%). Two hypersensitivity reactions to oxaliplatin also occurred. Conclusions: In this heavily pretreated patient population with PRR OVCA, this modified FOLFOX6 regimen exhibited a promising activity with an expected, but acceptable safety profile and might deserve further exploration, maybe in combination with biological or targeted agents. Clinical trial information: NCT01481701.