The peritoneal cancer index (PCI) calculated during exploratory laparotomy is a strong prognostic factor for overall survival (OS) in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). Progression of the PCI between diagnostic laparoscopy (DLS) and potential CRS + HIPEC (ΔPCI) might be a more dynamic prognostic factor for OS after CRS + HIPEC. Between 2012 and 2018, all colorectal PM patients who underwent an exploratory laparotomy for potential CRS + HIPEC after DLS were retrospectively identified from a prospectively maintained database. Patients were divided into stable disease (ΔPCI 0–3), mild progression (ΔPCI 4–9), or severe progression (ΔPCI ≥10). Kaplan–Meier analysis and a multivariate Cox regression were performed. Eighty-four patients (ΔPCI 0–3, n = 35; ΔPCI 4–9, n = 34; and ΔPCI ≥10, n = 15) were analysed. Median OS after CRS + HIPEC was significantly decreased in patients with a ΔPCI of 4–9 (35.1 95% CI 25.5–44.6) or ΔPCI ≥10 (24.1 95% CI 11.7–36.5) compared to patients with a ΔPCI of 0–3 (47.9 95% CI 40.0–55.7, p = 0.004). In multivariate regression analysis, ΔPCI remained an independent risk factor for OS: ΔPCI 4–9 HR 3.1 (95% CI 1.4–7.2, p = 0.007) and ΔPCI ≥10 HR 4.4 (95% CI 1.5–13.1, p = 0.007). A high ΔPCI is an independent dynamic prognostic factor for OS and might reflect a more aggressive tumour biology in patients with colorectal PM. HIPEC surgeons should be aware of a high-ΔPCI-associated diminished prognosis and should reconsider CRS + HIPEC when confronted with a ΔPCI ≥10.