His visit comes two days after Colombia's government and the country's last active guerrilla group, the ELN, announced a ceasefire, a key step toward sealing a "complete peace" to end Latin America's longest civil war.
"Peace is what Colombia has sought for a long time, and she is working to achieve it: a stable and lasting peace, so that we see and treat each other as brothers and not as enemies," the pope said in a video message on Monday.
"Peace reminds us that we are all children of the same Father, who loves and consoles us," he said ahead of the five-day tour, which will see him meet both those persecuted and their tormentors.
The Colombian conflict has left 260,000 people confirmed dead, 60,000 unaccounted for and seven million displaced.
Efforts to break the bloody cycle have proved controversial: Colombia's biggest guerrilla group, the FARC, disarmed under a historic peace accord, but critics say the rebels are getting off too lightly.
Colombians narrowly rejected the peace deal in a referendum last year.
The pontiff had tried unsuccessfully to mediate between President Juan Manuel Santos and the lead opponent of the accord, conservative leader Alvaro Uribe.
Santos and the FARC then tweaked their agreement and the government pushed it through congress in spite of continuing resistance from Uribe's side.
Testimony from survivors, oppressors
Vatican experts said Francis would be walking a diplomatic tightrope on the trip between calls for justice and mercy.
"Church officials are insisting Francis isn't going (to Colombia) to support the agreement itself," said Ines San Martin, correspondent for the specialist religious website Cruxnow.com.
"A distinction must be made between the common desire for peace and the signing of the agreement," she wrote.
The 80-year old Argentine, who will be making his 20th foreign trip as pope and fifth to his native Latin America, will touch down late afternoon Wednesday in Bogota, where he will be serenaded by traditional musicians.
There he will meet with Santos and leaders of the Catholic Church in Venezuela who have been attempting to help mediate in their country's crisis.
Based at the Vatican mission in the capital city, Francis will then make daily excursions by plane to the cities of Villavicencio, Medellin and Cartagena.
In Villavicencio, he will beatify two Catholic priests killed during the conflict, before presiding over a prayer for national reconciliation with victims of violence, former guerrilla members and ex-military fighters.
On stage with Francis will be the Bojaya Crucifix, which was badly damaged in a 2002 explosion in a church where hundreds of people had sought refuge from fighting. At least 79 of those sheltering inside were killed.
The pontiff will also meet with orphans in Medellin, considered the cocaine capital of the world during the reign of ruthless 1980s drug-kingpin Pablo Escobar.
Despite security concerns, Francis will ride around in three locally made, non-bullet-proof Popemobiles and is expected to embrace people in the crowds as on previous trips to Bolivia, Brazil, Cuba, Ecuador and Mexico.
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