Background: Double regimens are commonly accepted for AGC in East Asia. However, triple regimens are recommended in west countries. POF regimen (reported in 2007, 2008, 2009, 2010 ASCO) appeared to be of good efficacy and was well tolerated in patients with AGC. Intraperitoneal paclitaxel showed high local concentration in abdominal cavity and low systemic toxicity. The aims of this study were to find out if the POF and IP PAC was more effective with manageable side effects than FOLFOX in AGC (reported in 2017 ASCO-GI for feasibility analysis). Methods: The patients with AGC were randomized to three groups. The POF consisted of a 3-hour infusion of paclitaxel 135 mg/m², followed by FOLFOX omitted 5-Fu bolus. The IP PAC consisted of paclitaxel 80 mg/m2 intraperitoneally plus FOLFOX. Every 14 days repeated for all three regimens. Up to 9 cycles of treatment were administered, followed by S-1 until disease progression. The primary endpoint was PFS. Results: Between Nov 2015 and May 2018, 89 pts (30 POF, 29 IP PAC, 30 FOLFOX) were randomly allocated. PFS, OS and RR were seen in the table below. POF was better in PFS and RR than FOLFOX, although no statistically significant difference in RR. IP PAC was trend to be better in PFS than FOLFOX, but not in RR. OS was unmatured. The most common adverse events of grade 3 or 4 were neutropenia and neuropathy, but no significant difference among three groups. Conclusions: Both POF and IP PAC improved survival compared to FOLFOX. Only POF, not IP PAC, improved response rate compared to FOLFOX. Clinical trial information: NCT02845908