Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) represents a novel approach to intraperitoneal chemotherapy. Hereby results, obtained with PIPAC in patients with advanced peritoneal metastasis (PM) from colorectal cancer (CRC), are presented. Data from CRC patients (n = 24) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 trials are reported. Oxaliplatin 92 mg/m2 was administered at 4-6-week intervals. A CE certified nebulizer was used to aerosolize the chemotherapeutics. Outcome criteria were objective tumor response, survival and adverse events. Retrospective analysis of 74 PIPAC procedures carried out in 24 consecutive patients with PM from CRC included from October 2015 to February 2019. Five patients had still the primary tumor in situ, and 22 patients had received palliative systemic chemotherapy. Nineteen patients completed more than two PIPAC procedures, and objective tumor response according to the histological Peritoneal Regression Grading Score (PRGS) was observed in 67% of the patients, while 21% had stable disease. Four patients (21%) had complete response (mean PRGS = 1 and negative cytology). We recorded a median survival of 37.6 (range 7.3-48.9) months from the time of PM diagnosis, whereas it was 20.5 (range 0.13-34.7) months following the first PIPAC session. Minor postoperative complications were noted, and few were considered causally related to the PIPAC treatment. However, two cases of severe postoperative complications were recorded (urosepsis and iatrogenic bowel perforation). PIPAC with low-dose oxaliplatin can induce objective tumor regression in selected patients with advanced PM from colorectal cancer.