Background: Both Folfirinox and Nab-paclitaxel plus Gemcitabine showed a benefit in terms of survival in first-line treatment of metastatic pancreatic adenocarcinoma (MPA) when compared to gemcitabine. It could be of interest to use them consecutively, knowing that there is currently no standard for 2^nd line treatments for MPA and that median Progression free survival (PFS) is consistently less than 4 months in this setting. The aim of this study was to evaluate the efficacy and tolerability of gemcitabine plus Nab-paclitaxel after Folfirinox failure in MPA. Methods: From February 2013 to July 2014, all consecutive patients (pts) from 12 French centers treated by Nab-paclitaxel plus Gemcitabine for a histologically proven MPA after failure of Folfirinox were prospectively recorded. Nab-paclitaxel plus Gemcitabine was delivered on days 1, 8, and 15 every 4 weeks, as previously reported, until disease progression, patient refusal or unacceptable toxicity Results: Nab-paclitaxel plus Gemcitabine was administered to 57 pts. They received a median number of 4 cycles (1–12). Disease control rate was 58% (n = 33) with a 18.5 % (n = 18) objective response rate (RECIST). Within the whole cohort, median overall survival (OS) was 8.8 months (95% CI: 6.2-9.7) and median PFS was 5.1 months (95% CI : 3.2-6.2). Since the start date of first line chemotherapy with Folfirinox, median OS was 18 months (95% CI: 16-21). No toxic death occured. Grade 3–4 toxicities were reported in 40% of patients and were neutropenia (12%), neurotoxicity (12%), asthenia (8%) and thrombocytopenia (8%). Conclusions: With median PFS and OS of respectively 5.1 and 8.8 months Nab-paclitaxel plus Gemcitabine seems promising with a manageable toxicity profile after folfirinox failure, in selected patients able to receive second line treatment for a MPA. These promising results have now to be confirmed in a phase III randomized trial.