4134 Background: Despite the limited number of published RCTs, patients with resectable pancreatic adenocarcinoma (rPAC; NCCN criteria) seem to benefit from neoadjuvant (NAT) with regards to R0 resection rate, downstaging and survivals (PREOPANC-1; Preop-02/JSAP-05; NEONAX, SWOG05-15). Few prospective results are currently available concerning the completion of the full therapeutic sequence and oncological results. Methods: In the PANACHE01-PRODIGE48 prospective multicenter controlled non-comparative Phase II trial, 153 patients with rPDAC were randomized 2:2:1 to 4 cycles of NAT chemotherapy (mFOLFIRINOX; Arm1 or FOLFOX; Arm2) or upfront surgery (Ctrl_Arm) in 28 French centers from 02/2017 to 07/2020. Primary objective was to evaluate the safety and efficacy of two regimens of NAT chemotherapy. The main co-primary endpoints were 1y-OS rate after randomization and the rate of patients undergoing the full therapeutic sequence. Event-free survival (EFS) was used to evaluate the time to recurrence between groups. An event being defined as progression before surgery, unresectable or metastatic disease at surgical exploration, recurrence after surgery or death. Results: Of the 153 randomized patients, 146 were available for analysis (Arm1,n=70; Arm2,n=50; Ctrl_arm,n=26). In the Arm1 and 2, completion of the 4 planed cycles was 88.6 and 84%, respectively, with a dose reduction in 52% and 24%. The cumulative rates of grade 3/4/5 toxicity were 56.7 and 57.4%, respectively. The resection rates (RR) were 74, 68 and 81% respectively in Arm1, Arm2 and Ctrl_Arm. Respectively, 88.4, 91 and 85.7% of patients started adjuvant chemo. 1y-OS rates were respectively of 84.1, 71.8 and 80.8% in Arm1, Arm2 and Ctrl_Arm with a median follow-up in each group of 25.6, 33, 30.9 months. Following the intermediate analysis, the Arm2 was stopped for lack of efficacy (rejection of the H0 hypothesis for 1yOS). 1y-Event free survival (EFS) rates were 51.4% in Arm1, 43.1% in Arm2 and 41.7% in Ctrl_Arm, with corresponding median EFS of 12.4, 11 and 9.2 months. Conclusions: The feasibility and efficacy of the mFOLFIRINOX neoadjuvant chemotherapy is confirmed regarding completion of therapeutic sequence and oncological outcomes. These results confirm the rationale for ongoing clinical trials, PREOPANC3 and Alliance AO21806. Clinical trial information: NCT02959879.