Study of PI3Kinase Inhibition (Copanlisib) and Anti-PD-1 Antibody Nivolumab in Relapsed/Refractory Solid Tumors With Expansions in Mismatch-repair Proficient (MSS) Colorectal Cancer

Inclusion Criteria: * Age ≥18 years. * Ability to understand and willingness to sign a written informed consent document. * Phase I: Must have received all curative treatment options and at least 2 lines of systemic therapy. * Phase II: Must have received at least 2 lines of systemic therapy including a fluoropyrimidine, oxaliplatin, and irinotecan-containing regimen. KRAS/NRAS/BRAF wildtype patients must have received or refused anti-EGR. * Must have received all curative treatment options and at least 2 lines of systemic and standard therapy. * Must have measurable disease based on RECIST 1.1 * Must have biopsiable disease. * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Life expectancy of greater than 3 months. * Patients must have adequate organ and marrow function defined by study-specified laboratory tests within 21 days of initial study drug. * Men must use acceptable form of birth control while on study. * Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol. Exclusion Criteria: * Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti- PD-L2, anti-CTLA4, etc.). * Prior therapy with a PI3K inhibitor * Chemotherapy, target small molecule therapy, investigational therapy, or surgery within 4 weeks prior to first dose of treatment. * Has received prior radiotherapy within 2 weeks prior to the start of treatment. * Patient who is receiving or have received any other investigational agents within 4 weeks prior to the first dose of treatment. * Has received a live vaccine 30 days prior to the first dose of study drug. * Has known additional malignancy that is progressing or requires active treatment.. * Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has symptomatic ascites or has required a paracentesis in the last 12 weeks. * Hypersensitivity reaction to study drug. * Patients diagnosed of immunodeficiency or are on any immunosuppressive agents within 7 days prior to first dose of study drug. * Has active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Infection with HIV or hepatitis B or C. * Cytomegalovirus polymerase chain reaction (CMV PCR) positive. * Known history or concurrent interstitial lung disease. * Type I diabetes or Type II diabetes requiring treatment with a sulfonylurea, meglitinide, or insulin at screening. * Uncontrolled cardiovascular disease. * Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Use of anti-arrhythmic therapy (beta blockers or digoxin are permitted). * Use of CYP3A4 inhibitors and inducers within 2 weeks of starting study drug and throughout treatment. * Any arterial or venous thrombotic or embolic events within 3 months of start of study drug. * Non-healing wound, ulcer, or fracture. * Patients with evidence or history of bleeding condition. * Had a blood or platelet transfusion within 7 days of Cycle 1 Day 1 treatment. * Seizure disorder requiring anti-seizure medication. * Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures. * Are pregnant or breastfeeding. * Unwilling or unable to follow the study schedule for any reason.