Background: Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/GEJ adenocarcinoma. Previously, anthracycline based triplets have been aborted due to lack of efficacy and toxicity. We hypothesize that the combination of FOLFOX and nab-paclitaxel (FOLFOX-A) will have a higher efficacy, a better tolerability, and enhanced patient reported outcomes. Methods: Phase II single arm trial of FOLFOX + nab-paclitaxel in chemotherapy–naïve unresectable, advanced gastric/GEJ adenocarcinoma. Nab-paclitaxel 150 mg/m2 · Oxaliplatin 85 mg/m2 · Leucovorin 400 mg/m2 · 5-FU 2400 mg/m2 over 46-48 hrs every 14 days. Primary objective was response rate.Evaluable disease according to RECIST v1.1 for solid tumors was required. Her-2 positive gastric tumor patients and those with clinically significant peripheral neuropathy were excluded. A Simon (1989), optimal two-stage design was employed. Response rates and Clopper-Pearson confidence intervals are reported. Progression free (PFS) and overall (OS) survival were estimated using the method of Kaplan-Meier. Results: A 29% response rate was observed in Stage 1 and therefore the study continued enrolling all planned 39 patients. Median age was 63 (range 20-80) years, 29 (74%) were male, 30 patients now are off treatment due to progression (17), initiation of alternative therapy (5) and side effects (3). 38 patients started treatment. Of the 35 patients evaluable for response, 14 (40.0%; 95%CI: 23.9% - 57.9%) had CR/PR as best response, with disease control rate of 80.0%. Progression-free (PFS) and overall survival (OS) were available for 36 patients, with median follow-up duration of 20 months (range: 1.9 - 34.45 months). Median PFS was 6.6 months (95%CI: 5.7 – 13.0), with 28.6% (95%CI: 15.2% - 53.9%) 12-month PFS rate. There were 21 deaths, median OS was 11.0 months (95%CI: 9.6 – 21.7), 12-month OS rate was 46.6% (95%CI: 30.9% - 70.3%). Treatment-related grade 3–4 toxicities included peripheral sensory neuropathy, anemia (18.4% each), decreased neutrophil count (15.8%), and diarrhea (7.9%). One patient died due to multi-organ failure, not treatment-related. 23 patients required dose reductions or discontinuation of at least 1 component of the 3-drug regimen due to toxicity. Median number of cycles completed was 4 (range: 0-30). Conclusions: FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.