Background: Peritoneal metastasis (PM) still remains a major obstacle in the treatment of stage IV gastric cancer. This study was designed as a dose-escalation study of intraperitoneal (IP) paclitaxel combined with intravenous (IV) fluorouracil, leucovorin, and oxaliplatin (FOLFOX) to determine the recommended phase II dose in gastric cancer patients. Methods: Patients with gastric adenocarcinoma with PM were enrolled. Peritoneal cancer index (PCI) score was evaluated, and IP + IV chemoport insertion was done. The initial dose of IP paclitaxel was 40mg/m², then stepped up to 60 then 80mg/m². Target dose was 100mg/m². IV FOLFOX was administered on the same day (oxaliplatin 100mg/m², leucovorin 100mg/m², fluorouracil 2400mg/m²). Dose limiting toxicity (DLT) was defined as leukopenia ≥ grade 4, thrombocytopenia ≥ grade 3, febrile neutropenia ≥ grade 3, and other nonhematologic toxicity ≥ grade 3. Results: Fifteen patients were enrolled, and two patients were dropped due to patient consent withdrawal. There was no DLT at 40 and 60mg/m² doses. Two patients had grade 3 febrile neutropenia at dose 80mg/m², and thus the final recommended phase II dose was 60mg/m². Other patients underwent IP paclitaxel and FOLFOX without serious adverse events. Seven patients underwent second-look diagnostic laparoscopy, and the average change in PCI score was -5.6 ± 9.3. Four patients received gastrectomy, and the ascites conversion rate was 4/5 (80%). Median survival time was 16.6 months (95% CI, 7.2 – N/A). Conclusions: The biweekly regimen of IP paclitaxel and FOLFOX is safe and the recommended dose for a phase II trial is 60mg/m². Clinical trial information: NCT03618758.