This study is an interventional open label prospective study that aims to assess both overall and disease-free survival of patients treated with LDLT, partial or whole graft LT from deceased donors for unresectable CRLM.

Secondary outcomes are graft survival and donor outcomes in terms of safety and quality of life.

Donor selection is performed according to the currently used Institutional and National standards and protocols.

Liver Transplant (LT) is a feasible, safe and effective curative strategy for patients with unresectable colorectal liver metastases (CRLM), and several trials are currently active and in a recruitment phase to study its impact with both conventional donors and living donors (LDLT).

As a matter of fact, in this setting living donors represent a helpful resource, thanks to the opportunity to schedule the LT at the timeliest conditions in terms of oncological response and patient's performance status. LDLT is a well-established procedure that is already offered to patients listed for LT at our Institution.

Crucial requirement for study eligibility is the assessment of non-resectability of the presented liver metastases from colorectal cancer (CRC).

Criteria for non-resectability of the liver-only CRC metastases eligible for the study should be assessed at the patient study entry, by the surgeon in charge together with the multidisciplinary team.

Patients fulfilling the inclusion criteria of the study will undergo clinical, translational and regulatory steps. Briefly, the main procedures and requirements of the study can be summarized as follows:

- Pre-transplant screening and waiting phase:

Screening of patients with liver-limited CRC metastases potentially eligible to the study will be registered. The screening for general eligibility to liver transplantation will be conducted according to the existing Institutional protocol (called in Italian "PDTA", "Percorso Diagnostico Terapeutico Assistenziale").

During screening or waiting time periods, patients will continue planned chemotherapy treatment and will undergo blood tests (including CEA and Ca19.9), thoraco-abdominal CT scan and positron emission tomography (PET) scan (if needed) every 8 weeks.

- Donors' screening:

Screening of donors will be held according to the existing Institutional protocol for LDLT

- Informed consent:

Consent to the study will be signed after completion of the pre-LT screening, that is once co-morbidities and transplant eligibility will be ascertained on top of cancer conditions. In addition, patients will have to sign additional written informed consent prior to any study procedure.

- Post-transplant follow-up:

Following LDLT, standard institutional follow-up procedures will be performed and registered. Patient/graft condition and tumor status should be re-assessed at least every 4 months for the first 3 years, every 6 months for the rest of follow-up.

Following donation standard institutional follow up will be performed on donors and registered.

Inclusion Criteria:

• Age ≥18.
• Histologically confirmed colon and rectum (intraperitoneal) adenocarcinoma.
• Pathological classification of primary tumor as pT1-3, without peritoneal tumor deposits, absence of mucinous component >50%, confirmed R0 resection, no limitations for RAS mutations, B-RAF wild type.
• No signs of extra hepatic metastatic disease or local recurrence according to CT scan+MRI+PET/CT scans.
• Liver metastases not eligible for curative liver resection
• Objective response according to RECIST 1.1 to first-line treatment, with sustained response for at least 4 months, OR disease control (complete [CR] or partial response [PR] or standard disease [SD]) during second- line treatment for at least 4 months.
• Carcinoembryonic Antigen (CEA) values stable or decreasing during the enrollment prior to liver transplant.
• Performance status, ECOG (Eastern Cooperative Oncology Group) 0-2.
• Signed informed consent and expected cooperation of the patients for the treatment and follow-up, and national/local regulations.

Exclusion Criteria:

• Hereditary CRC syndromes including FAP (Familial adenomatous polyposis) and Lynch syndrome.
• Prior extra hepatic metastatic disease or primary tumor local relapse.
• Palliative resection of primary CRC tumor.
• Disease progression
• Other malignancies in the previous 5 years (with exception of in situ cervical carcinoma and basal cell carcinoma; superficial bladder tumors are allowed if curatively treated).
• Active intra-venous or alcohol abusers (patients may be eligible if abstention > 6 months is demonstrated)
• Active HIV infection
• Psychiatric disorders and patient low compliance
• Any reason why, in the judgment of the investigators, the patient should not participate (to be formally declared)