Background: Postoperative chemotherapy (S-1, CAPOX, or Docetaxel/S-1) is a standard treatment for stage II/III gastric cancer in Asia. With regard to single agent or doublet, the need for improvement has consistently been pointed out because of the relatively poor outcome for patients with stage III gastric cancer. Triplet (FLOT) has shown significant survival benefits in perioperative setting. POF, our regiment similar to FLOT, demonstrated priority to doublet (FOLFOX) in advanced setting (2019 ASCO-GI). We conducted a randomized, multicenter, phase III study to compare triplet to doublet regimens for patients with stage III gastric cancer. Methods: This is currently enrolling patients (n = 544) with pathologic stage III gastric cancer after D2 lymph node dissection. Patients are randomized 1:1 and stratified by tumor stage (IIIA, IIIB, or IIIC, AJCC 8th) into POF or SOX/CAPOX/FOLFOX (chosen by the clinicians). SOX: oxaliplatin 130 mg/m2 on day 1, oral S-1 80mg/m2 divided by two on days 1 to 14 every 21 days for 8 cycles. CAPOX: oxaliplatin 130 mg/m2 on day 1, oral capecitabine 1000 mg/m2 twice daily on days 1 to 14 every 21 days for 8 cycles. FOLFOX: oxaliplatin 85 mg/m2, levo-leucovorin 200 mg/m2, and 5-FU 400 mg/m2 bolus on day 1, then 5-FU 2400 mg/m2 continuous infusion over 46 hours, every 14 days for 12 cycles. Three doublets were chosen by the clinicians. POF: paclitaxel 135 mg/m2, followed by FOLFOX omitted 5-FU bolus, every 14 days for 12 cycles. Eligibility criteria: patients aged 18-70 years, primary histologically proven gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) of stage III with no evidence of metastatic disease, R0 resection with D2 lymph node dissection, good performance status (ECOG PS ≤1). Subjects must be able to take orally, and without other concomitant medical conditions that required treatment, initially treated with curative surgery followed by chemotherapy within 42 days. Life expectancy estimated more than 6 months. Adequate organ function. All patients provided written informed consent prior to treatment. Key exclusion criteria: patients with other primary malignancies, gastrointestinal bleeding. The primary end point is 3-year disease-free survival. Secondary end points are 3-year overall survival, 5-year overall survival, 5-year disease-free survival, and adverse events. Clinical trial information: NCT03788226.