This is a phase III randomized, multicenter study with two different arm:

• experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin
• comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility.

Patient will be randomized in a 1:1 ratio. Randomization will be done during surgery if the total resection of tumour will be reached and will use a stratification procedure based on center

This is a phase III randomized, multicenter study with two different arm:

• experimental: prophylactic surgery plus HIPEC CO2 performed with mitomycin
• comparator: standard surgery Adjuvant treatment after surgery is mandatory except for documented cases of non-eligibility.

Patient will be randomized in a 1:1 ratio. Randomization will be done during surgery if the total resection of tumour will be reached and will use a stratification procedure based on center

The HIPEC CO2 regimen will be as reported below:

mitomycin: (total dose of 35 mg/mq, physiologic solution 0.9%) administrated 50% at time 0 from start of HIPEC CO2 treatment (17.5 mg/mq), 25% (8.8 mg/mq) after 30 minutes and the last dose 25% after 60 minutes. Recommended temperature for HIPEC treatment is 41-42 °C for 90 minutes.

Adjuvant treatment consists of a 6 months chemotherapy after surgery. It is possible to choose between Oxaliplatin, Capecitabine (XELOX) or Oxaliplatin, Fluorouracil, Leucovorin (FOLFOX-4) Patients affected by CRC at high risk of developing peritoneal carcinomatosis will be randomized in the study.

Inclusion Criteria:

1. Patients with histologically documented colorectal adenocarcinoma eligible for R0,

   1. Presurgical or intraoperative stage T4a or T4b primary tumour (TNM 8 th)
   2. Urgent presentation: perforation without purulent generalized peritonitis or fecal peritonitis
   3. Peritumoral minimal peritoneal carcinomatosis: limited peritoneal disease in close proximity to the primary tumour, that may be removed en bloc
   4. Ovarian metastases (Krukenberg tumor)

2. Age ≥ 18 and ≤75 years

3. Written informed consent

Exclusion Criteria:

1. Distant metastatic disease (even if limited and completely resected)
2. History of tumour diagnosed in the 3 years before entering the study, except for topical and healed pathologies that do not need further treatment (e.g. non-melanoma skin carcinomas, superficial bladder carcinomas or in situ carcinoma of the breast or cervix).
3. Psychological, family or social conditions which may negatively affect the treatment and follow-up protocol.
4. Poor general conditions (ECOG > 2).
5. Impaired cardiac function (history of congestive heart failure or FE <40%). Clinically significant cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrolment), myocardial infarction (<6 months prior to enrolment), unstable angina, congestive heart failure (New York Heart Association Classification Class > II or serious uncontrolled cardiac Arythmia requiring medication
6. Impaired renal function (creatinine> 1.5 upper limit of normal or creatinine clearance <60 mL / min)
7. Impaired hepatic function (AST, ALT >2.5 upper limit of normal, bilirubin> 1.5 upper limit of normal)
8. Impaired hematopoietic function (leucocytes <4000 / mm3, neutrophils <1500 / mm3, platelets <100000 / mm3)
9. Impaired pulmonary function (presence of COPD or other pulmonary restrictive conditions with FEV1 <50% or DLCO <40% of normal age value).
10. Pregnancy
11. History or presence of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of HIPEC or chemotherapy or patient at high risk from treatment complications.
12. Chronic inflammatory bowel disease
13. Patients with acute bowel obstruction
14. Refusal to join the study