It was not immediately clear who was responsible for the shooting.
In a condolence message sent on Friday to the Egyptian president, Francis said he'll continue his "intercession for peace and reconciliation" throughout Egypt. The head of the Coptic church, Pope Tawadros II, has vocally supported el-Sisi's government for its promise of security and stability.
Eyewitnesses said masked men opened fire after stopping the Christians, who were in a bus and other vehicles.
For years, Islamic militants have been waging an insurgency mostly centred in Egypt's Sinai Peninsula, though a growing number of attacks have recently also taken place on the mainland.
This has not been the first time Coptic Christians have been the targets of violence.
The country's Christians have complained that the government is not doing enough to protect them from Islamic extremists, and hundreds of them reacted to the bus attack by staging angry street protests in two provincial cities, destroying at least six cars and briefly cutting off railway lines.
The same source, speaking on condition of anonymity, said the ill-fated bus had been traveling from Beni Sueif to the monastery, located roughly 220 kilometers south of Cairo.
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But he said they initially may not have realized they were a target of Russian intelligence services. Brennan said it was possible for someone to be helpful to the Russian cause without realising it.
Copts have been targeted outside Egypt as well: In early 2015, a highly produced ISIS propaganda video purported to show the beheadings of over a dozen Egyptian Copts on a beach in Libya.
"Church officials say children and elderly people are among" the victims, Jane adds.
After the latest attack, Sissi called an emergency meeting of security officials, state-run media reported. The attacks left over 75 dead and scores wounded.
Egypt's Coptic Orthodox Church said it was "in pain along with the nation over violence and evil" as it paid condolences to the families of the victims.
There was no immediate claim of responsibility, but the Islamic State has claimed responsibility for previous attacks against Egypt's Christians, which comprise about 10 percent of the population.
Germany also condemned the attack, with a spokesman for the Foreign Ministry in Berlin calling it "simply a tragedy".
Activists monitoring the plight of Coptic Christians in Egypt said that the attack targeted a private auto, a bus and a truck as they drove along an unpaved desert road en route to the monastery of Saint Samuel, located close to Maghagha in the province of Minya, roughly 220km south of Cairo. However, no group has yet claimed responsibility.